Constriction Of Inferior Vena Cava Research Articles

Pentobarbital anesthesia alters pulmonary vascular response to neural antagonists

We investigated the effects of pentobarbital sodium anesthesia on vasoregulation of the pulmonary circulation. Our specific objectives were to 1) assess the net effect of pentobarbital on the base-line pulmonary vascular pressure-to-cardiac index (P/Q) relationship compared with that measured in conscious dogs, and 2) determine whether autonomic nervous system (ANS) regulation of the intact P/Q relationship is altered during pentobarbital. P/Q plots were constructed by graded constriction of the thoracic inferior vena cava, which produced stepwise decreases in Q. Pentobarbital (30 mg/kg iv) had no net effect on the base-line P/Q relationship. In contrast, changes in the conscious intact P/Q relationship in response to ANS antagonists were markedly altered during pentobarbital. Sympathetic alpha-adrenergic receptor block with prazosin caused active pulmonary vasodilation (P less than 0.01) in conscious dogs but caused vasoconstriction (P less than 0.01) during pentobarbital. Sympathetic beta-adrenergic receptor block with propranolol caused active pulmonary vasoconstriction (P less than 0.01) in both groups, but the magnitude of the vasoconstriction was attenuated (P less than 0.05) during pentobarbital at most levels of Q. Finally, cholinergic receptor block with atropine resulted in active pulmonary vasodilation (P less than 0.01) in conscious dogs, whereas vasoconstriction (P less than 0.01) was observed during pentobarbital. Thus, although pentobarbital had no net effect on the base-line P/Q relationship measured in conscious dogs, ANS regulation of the intact pulmonary vascular P/Q relationship was altered during pentobarbital anesthesia.

Combined neurohumoral block modulates pulmonary vascular P/Q relationship in conscious dogs.

Our objective was to investigate the integrated pulmonary vascular response of conscious dogs to combined inhibition of the autonomic nervous system, arginine vasopressin (V1) receptors (vasopressinergic V1), and converting enzyme to identify the overall influence of these three major neurohumoral mechanisms in vascular regulation of the pulmonary circulation. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were generated by graded constriction of the thoracic inferior vena cava, which produced stepwise decreases in Q. When compared with the P/Q relationship measured in intact conscious dogs, combined neurohumoral block resulted in active, nonflow-dependent pulmonary vasodilation. A second objective was to assess the extent to which cyclooxygenase pathway inhibition modified both the intact P/Q relationship and the pulmonary vasodilator response to combined neurohumoral block. Cyclooxygenase inhibition alone (either indomethacin or sodium meclofenamate) resulted in active, nonflow-dependent pulmonary vasoconstriction. Moreover, the pulmonary vasodilation in response to combined neurohumoral block was entirely abolished following cyclooxygenase inhibition. Thus the integrated pulmonary vascular response of conscious dogs to combined neurohumoral block is active vasodilation. This response appears to be mediated by metabolites of the cyclooxygenase pathway.

Absence of neural modulation of hypoxic pulmonary vasoconstriction in conscious dogs.

Our objectives were 1) to quantify the magnitude of the hypoxic pulmonary vasoconstrictor (HPV) response in conscious dogs by utilizing pulmonary vascular pressure-cardiac index (P/Q) plots and 2) to assess the extent to which the autonomic nervous system (ANS) modulates the HPV response. Multipoint P/Q plots were constructed in conscious dogs during normoxia and during bilateral alveolar hypoxia by stepwise constriction of the thoracic inferior vena cava to reduce Q. With the ANS intact, the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) increased (P less than 0.01) approximately twofold during hypoxia over a broad range of Q. The absolute magnitude of the HPV response was related (P less than 0.01) to the level of Q. We hypothesized that if ANS activation reduces the magnitude of HPV in intact dogs, then we would expect the magnitude of HPV to be increased both after combined sympathetic alpha-(phentolamine) and beta-(propranolol) adrenergic block and after total autonomic ganglionic block (hexamethonium). A marked HPV response (P less than 0.01) was observed after both combined sympathetic block and ganglionic block over a broad range of Q during alveolar hypoxia. The magnitude of the HPV response with the ANS intact, however, was not significantly different from the magnitude of HPV after combined sympathetic block (P = 0.45) or after ganglionic block (P = 0.64) at any level of Q. Thus, during bilateral alveolar hypoxia, the ANS does not appear to attenuate the HPV response of intact conscious dogs.

Plasma atrial natriuretic factor during chronic thoracic inferior vena caval constriction.

The effects of chronic constriction of the thoracic inferior vena cava (TIVCC) on plasma atrial natriuretic factor (pANF) were studied in conscious dogs (n = 5). TIVCC decreased left and right atrial pressure and led to a decrease in pANF concentration from 199 +/- 12 to 104 +/- 14 pg/ml while plasma renin and vasopressin concentrations increased. These hormonal changes were associated with a significant fall in sodium excretion to less than 5 meg/day. pANF remained suppressed during chronic TIVCC as the dogs expanded their extracellular fluid volume and developed ascites. Acute release of TIVCC resulted in abrupt increases in left and right atrial pressure but only a modest rise in pANF from 96 +/- 16 to 185 +/- 45 pg/ml. The magnitude of the rise in pANF (twofold) contrasted sharply with the eightfold increase in sodium excretion that occurred over the first 24 hours. Our data suggest that decrease in atrial pressure below normal results in a decline in pANF, which, acting in concert with the activated renin-angiotensin system and vasopressin, may contribute to sodium retention. On the other hand, during acute release of TIVCC, which markedly increased atrial pressure and sodium excretion, pANF only returned to control levels. These data suggest that ANF release may be attenuated during chronic reduction in atrial pressure and also raise a question concerning the magnitude of the primary role of ANF in this natriuretic response.

AVP-induced pulmonary vasodilation during specific V1 receptor block in conscious dogs

Our objectives were 1) to determine whether exogenously administered arginine vasopressin (AVP) can exert a vasoactive influence on the pulmonary circulation of conscious dogs during specific vasopressinergic-1 (V1) receptor block, and 2) to assess the extent to which the pulmonary vascular response to AVP during V1 receptor block is mediated by either sympathetic beta-adrenergic or cholinergic receptor activation or by cyclooxygenase pathway activation. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by stepwise constriction of the thoracic inferior vena cava to reduce Q. In dogs pretreated with a specific V1 receptor antagonist [d(CH2)5 AVP, 10 micrograms/kg iv], AVP infusion (7.6 ng.kg-1 X min-1 iv) increased (P less than 0.01) Q from 139 +/- 6 to 175 +/- 8 ml.min-1 X kg-1, and decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure: PAP-PCWP) over the entire range of Q studied (140 to 80 ml.min-1 X kg-1). This pulmonary vasodilator response to AVP during V1 block was also observed following sympathetic beta-adrenergic block alone, following combined sympathetic beta-adrenergic and cholinergic block, and following cyclooxygenase pathway inhibition. Thus exogenous administration of AVP during specific V1 receptor block results in active, nonflow-dependent pulmonary vasodilation. This pulmonary vasodilator response is not mediated by reflex activation of sympathetic beta-adrenergic or cholinergic receptors or by metabolites of the cyclooxygenase pathway over a broad range of Q.

Bradykinin actively modulates pulmonary vascular pressure-cardiac index relationships.

Our objectives were to investigate the pulmonary vascular effects of exogenously administered bradykinin at normal and reduced levels of cardiac index in intact conscious dogs and to assess the extent to which the pulmonary vascular response to bradykinin is the result of either cyclooxygenase pathway activation or reflex activation of sympathetic beta-adrenergic and -cholinergic receptors. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by step-wise constriction of the thoracic inferior vena cava to reduce Q. In intact dogs, bradykinin (2 micrograms X kg-1 X min-1 iv) caused systemic vasodilation, i.e., systemic arterial pressure was slightly decreased (P less than 0.05), Q was markedly increased (P less than 0.01), and mixed venous PO2 and oxygen saturation (SO2) were increased (P less than 0.01). Bradykinin decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) over the entire range of Q studied (140-60 ml X min-1 X kg-1) in intact dogs. During cyclooxygenase pathway inhibition with indomethacin, bradykinin again decreased (P less than 0.05) pulmonary arterial pressure-pulmonary capillary wedge pressure at every level of Q, although the magnitude of the vasodilator response was diminished at lower levels of Q (60 ml X min-1 X kg-1). Following combined administration of sympathetic beta-adrenergic and -cholinergic receptor antagonists, bradykinin still decreased (P less than 0.01) pulmonary arterial pressure-pulmonary capillary wedge pressure over the range of Q from 160 to 60 ml X min-1 X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

NEURAL REGULATION OF THE PULMONARY CIRCULATION FOLLOWING SYSTEMIC HYPOTENSION IN CONSCIOUS DOGS

To investigate autonomic nervous system (ANS) regulation of the pulmonary vascular response to increasing cardiac index (CI:ml/min/kg) following systemic hypotension (H), the pulmonary vascular pressure gradient (pulmonary arterial-pulmonary capillary wedge pressure: ΔP) was measured at multiple levels of CI during stepwise inflation and deflation of an inferior vena cava (IVC) occluder. In intact dogs, maximum IVC constriction decreased (p<0.01) CI from 139±9 to 46±3, and systemic arterial pressure from 108±2 to 55±3 mmHg. Following 15 minutes of H, CI was gradually increased by deflation of the IVC occluder. Surprisingly, ΔP was not significantly changed at any level of CI following H in intact dogs or after cholinergic block (atropine 0.1 mg/kg). In contrast, β adrenergic block (propranolol 1 mg/kg) increased ΔP at every level of CI following H, e.g. at CI = 100, ΔP was increased (p<0.01) 16±2% from 10.2±0.5 mmHg. Pulmonary vasoconstriction following H was not observed during total autonomic ganglionic block (hexamethoniura 30 mg/kg), i.e. AP at CI - 100 was slightly decreased (p<0.05) 6±2% from 9.7±0.8 mmHg following H. These results suggest that the pulmonary circulation is actively modulated by the ANS following H. ANS-mediated vasodilator and vasoconstrictor influences appear to offset one another in the intact and cholinergic blocked conscious dog.

Assessment of left ventricular end-systolic pressure-volume relations with an impedance catheter and transient inferior vena cava occlusion: Use of this system in the evaluation of the cardiotonic effects of dobutamine, milrinone, posicor and epinephrine

The end-systolic pressure-volume relation has been postulated as a load-independent measure of cardiac contractility, but has been difficult to measure because of technical problems associated with the serial measurement of intracardiac volume over a physiologic range of ventricular loading conditions. Utilizing a multielectrode impedance catheter to assess continuous, on-line left ventricular relative volume during transient inferior vena cava occlusion, a method is described for determining the end-systolic pressure-volume relation and for assessing changes in this relation secondary to inotropic modulation. In particular, using this method, the relative inotropic properties were determined of four drugs: dobutamine, milrinone, epinephrine and an experimental cardiotonic agent (Ro 13-6438, Posicor). Left ventricular micromanometer pressure and impedance catheter volume were measured continuously in 10 open chest, anesthetized dogs and 14 pigs. Arterial pressure was altered over a range of 20 to 60 mm Hg by brief inferior vena cava constriction. A linear end-systolic pressure-volume relation was observed in pressure-volume diagrams constructed from on-line pressure and impedance catheter recordings. Administration of dobutamine, milrinone and epinephrine resulted in a leftward shift and an increase in the slope of the end-systolic pressure-volume relation as compared with baseline; Posicor did not alter the slope over a range of doses, despite an increase in the cardiac output secondary to arterial vasodilation. Volume changes as measured by the impedance method closely paralleled simultaneous changes in the ultrasonic crystal-determined segment length, and the impedance end-systolic pressure-volume relation slope was reproducible with repeated load-altering maneuvers.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary vasoactive effects of exogenous and endogenous AVP in conscious dogs.

Our objectives were to investigate the extent to which both exogenously administered and endogenously released arginine vasopressin (AVP) exert a direct, vasoactive influence on the pulmonary circulation of conscious dogs. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by stepwise constriction of the thoracic inferior vena cava (IVC) to reduce Q. In intact dogs, AVP infusion (7.6 ng X kg-1 X min-1 iv) increased (P less than 0.01) plasma AVP from 2.3 +/- 0.4 to 280 +/- 23 pg/ml, and increased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure minus pulmonary capillary wedge pressure, PAP-PCWP) over the entire range of Q studied. Following administration of autonomic nervous system antagonists and a converting-enzyme inhibitor, exogenous AVP again increased (P less than 0.01) PAP-PCWP over the entire range of Q. Generation of P/Q plots via IVC constriction resulted in systemic hypotension (58 +/- 4 mmHg) and a concomitant increase (P less than 0.01) in endogenous AVP release from 2.1 +/- 0.2 to 109 +/- 22 pg/ml. Following administration of the specific AVP receptor antagonist [d(CH2)5]AVP (10 micrograms/kg iv), systemic arterial pressure, but not PAP - PCWP, was decreased to significantly lower levels as Q was reduced during IVC constriction. A similar response was observed in dogs pretreated with the neurohumoral blockers. Thus exogenous administration of AVP results in active, non-flow-dependent pulmonary vasoconstriction. This effect is not dependent on reflex activation of the autonomic nervous system or on the increased production of angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary vascular responses to angiotensin II and captopril in conscious dogs

Our objectives were to investigate the extent to which angiotensin II (ANG II) and converting-enzyme inhibition (CEI) exert a direct vasoactive influence on the pulmonary circulation of conscious dogs. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by stepwise constriction of the thoracic inferior vena cava to reduce Q. The effects of ANG II infusion (60 ng X kg-1 X min-1, iv) and CEI with captopril (1 mg/kg plus 1 mg X kg-1 X h-1, iv) on pulmonary vascular P/Q plots were assessed first with the conscious dogs intact and again after combined administration of pharmacological antagonists to block sympathetic alpha- and beta-adrenergic, cholinergic, and arginine vasopressin receptors. In intact dogs, ANG II increased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure, PAP-PCWP) over the entire range of Q studied (60-120 ml X min-1 X kg-1). Conversely, CEI decreased (P less than 0.05) PAP-PCWP at each level of Q. After administration of the autonomic nervous system and arginine vasopressin receptor antagonists, ANG II again increased (P less than 0.01) and CEI decreased (P less than 0.01) PAP-PCWP over the entire range of Q studied. Thus exogenous administration of ANG II results in active, nonflow-dependent constriction of the pulmonary circulation, and this effect is not dependent on the autonomic nervous system or increased circulating levels of arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of vasopressin antagonist on water excretion in inferior vena cava constriction

Elevated levels of plasma arginine vasopressin (AVP) have been suggested to impair water excretion in congestive heart failure. In the present study, to determine a role for AVP in the impaired water excretion in rats with the inferior vena cava constriction (IVC), two AVP antagonists were used in the IVC rats at the proximal portion of the hepatic vein under the diaphragm and in sham-operated (control) rats. After surgery, 48 hrs were allowed before the experiments were started. A mean cardiac index of 260.0 +/- 12.3 ml/min/kg in the IVC rats was significantly lower than that in the control rats, 323.6 +/- 13.2 ml/min/kg (P less than 0.01). The rats were given an antidiuretic antagonist, [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-(O-ethyl)-D-tyrosine, 4-valine] AVP (30 micrograms/kg) or the antagonist vehicle, i.p., and 20 min later they were administered 30 ml/kg of water orally. Minimal urinary osmolality (Uosm) in the IVC rats receiving the vehicle was significantly greater than the control rats (292.7 +/- 53.1 vs. 97.8 +/- 10.6 mOsm/kg H2O, P less than 0.01). The administration of the antidiuretic antagonist in the IVC rats decreased minimal Uosm to 90.0 +/- 3.6 mOsm/kg H2O. This value was significantly lower than the vehicle rats (P less than 0.01), and was a comparable level to minimal Uosm of 82.1 +/- 3.7 mOsm/kg H2O in the control rats receiving the antidiuretic antagonist. The IVC rats excreted 51.4 +/- 5.9% of the water load in three hr, a value significantly less than that excreted by the control rats, 95.1 +/- 6.0% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

MRI of the Budd-Chiari syndrome

Five of six patients with angiographically proved Budd-Chiari syndrome (hepatic venous outflow obstruction) showed multiple specific MRI abnormalities: striking reduction in caliber or complete absence of the hepatic veins, "comma-shaped" intrahepatic collateral vessels, and/or marked constriction of the intrahepatic inferior vena cava. The sixth patient had angiographically proven sinusoidal hepatic venous obstruction and patent central hepatic veins; MRI showed ascites but revealed no specific features of the Budd-Chiari syndrome. Patients with end-stage cirrhosis also showed compressed, distorted hepatic veins; however, these cirrhotic livers were distinguished by their small size, nodular surface, and extrahepatic collateral varices. In patients without cirrhosis or the Budd-Chiari syndrome, normal hepatic, portal, and inferior caval veins were routinely seen when technically adequate MRI examinations were obtained (94 of 100 cases). Four of the six patients with Budd-Chiari syndrome had been treated surgically. In three, MRI identified patent portocaval shunts. In the fourth, angiographically confirmed shunt stenosis was demonstrated by MRI.

Neural antagonists modulate pulmonary vascular pressure-flow plots in conscious dogs.

Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed in conscious dogs during normoxia by graded constriction of the thoracic inferior vena cava to reduce Q. P/Q plots were generated with the autonomic nervous system (ANS) intact and following total autonomic ganglionic block, cholinergic block, and sympathetic alpha- and beta-adrenergic block alone and in combination. With the ANS intact, the relationship between the pulmonary vascular pressure gradient [pulmonary arterial pressure (PAP)--pulmonary capillary wedge pressure (PCWP)] and Q was linear with an extrapolated pressure intercept of 0 mmHg. Total autonomic ganglionic block increased PAP-PCWP over the entire range of Q studied (60-140 ml . min-1 . kg-1). Cholinergic block resulted in a small increase in PAP-PCWP at a Q of 60 ml . min-1 . kg-1, a small decrease in PAP-PCWP at a Q of 140 ml . min-1 . kg-1, but no change in PAP-PCWP over the midrange of Q. Sympathetic beta-adrenergic block increased, and sympathetic alpha-adrenergic block decreased PAP-PCWP over the entire range of Q studied. Combined sympathetic alpha- and beta-adrenergic block also increased PAP-PCWP at each level of Q. Thus the ANS, either directly or via circulating catecholamines, exerts an active regulatory influence on the pulmonary vascular P/Q relationship of intact conscious dogs during normoxia over a wide range of Q. Activation of sympathetic beta-adrenergic receptors results in pulmonary vasodilatation, whereas, alpha-receptor activation results in vasoconstriction. Surprisingly, based on the effects of total autonomic ganglionic block and combined sympathetic alpha- and beta-adrenergic block, the net effect of the ANS on PAP-PCWP/Q during normoxia appears to be pulmonary vasodilatation.

Ganglionic blockade in conscious dogs with chronic caval constriction.

Chronic constriction of the thoracic inferior vena cava decreases venous return and cardiac output, increases the secretion of renin and aldosterone, and produces sodium retention with ascites and edema formation. The arterial pressure is maintained at normotensive levels in this caval model by an increase in total peripheral resistance. The objective of the present study was to compare renal and hemodynamic responses to ganglionic blockade in the conscious thoracic caval dog to responses obtained in another low-output model, the chronic sodium-deplete dog, and also to the responses obtained in the normal sodium-replete dog. The control base-line pressures averaged 103 +/- 2, 110 +/- 3, and 110 +/- 3 mmHg, respectively, in the sodium-replete, sodium-deplete, and thoracic caval dogs (P greater than 0.05). Ganglionic blockade in the conscious dog with caval constriction resulted in a sustained 20- to 30-mmHg fall in the arterial pressure; a sustained fall of 20 mmHg occurred in the sodium-deplete dogs. In contrast, ganglionic blockade failed to decrease the blood pressure at any time in the normal sodium-replete animals. Effective renal blood flow and creatinine clearance failed to demonstrate sustained changes after ganglionic blockade in any group of dogs; renal sodium excretion increased only in the normal sodium-replete dogs. These results suggest an enhanced contribution of the sympathetic nervous system to blood pressure maintenance in both the sodium-deplete and the caval dogs. Although the data fail to demonstrate an important contribution of the adrenergic system in the chronic sodium retention in these two experimental models, decreases in renal perfusion pressure may have blunted any potential natriuresis in these animals following ganglionic blockade.

Multipoint pulmonary vascular pressure-cardiac output plots in conscious dogs.

To characterize quantitatively the relationships among pulmonary vascular pressures (P) and cardiac output (Q) in conscious dogs, multipoint plots of pulmonary arterial (PAP), pulmonary capillary wedge (PCWP), PAP - PCWP, and left atrial (LAP) pressure versus Q were generated by graded constriction of the thoracic inferior vena cava (IVC) to vary Q. Slopes and extrapolated pressure intercepts from linear regression fits to the P/Q plots were determined for three inspired oxygen tensions: normoxia, hyperoxia, and hypoxia. During normoxia (arterial Po2 87 +/- 1 Torr), the extrapolated pressure intercepts for PAP, PCWP, and PAP - PCWP were virtually 0 mmHg, and for LAP, substantially negative (-5.5 +/- 1.1 mmHg; P less than 0.01). Hyperoxia (Po2 365 +/- 28 Torr) had no effect on any of the P/Q plots. In contrast, hypoxia (Po2 51 +/- 1 Torr) significantly increased the intercepts (P less than 0.01) as well as the slopes (P less than 0.05) of PAP and PAP - PCWP versus Q, but produced only minor changes in PCWP and LAP versus Q. These hypoxia-induced changes in intercepts, perhaps related to changes in critical closing pressures, demonstrate the limitations of pulmonary vascular resistance calculations (quotient of pressure gradient and Q) in quantifying changes in pulmonary vasomotor tone. In this way, the IVC constriction technique provides a more complete description of P/Q relationships than that permitted by simple calculations of pulmonary vascular resistance. We conclude that this technique can be utilized to investigate the effects of other physiological and pharmacological interventions on pulmonary vasomotor tone in conscious dogs.

Hypothalamic neurons responding to hemodynamic input and to stimulation in the pons may influence adrenocorticotropin release

Experiments were designed to identify hemodynamically sensitive neurons in the mediodorsal hypothalamus and to determine if they were also sensitive to electrical stimulation of areas in the dorsal rostral pons that were implicated previously in the control of adrenocorticotropin (ACTH) release. Cats were anesthetized with chloralose and urethane, immobilized with gallamine, and artificially respired. Hemodynamic stimuli included constriction (CC) of the supradiaphragmatic inferior vena cava to reduce venous return and sinusoidal volume pulsation (RA) of the right atrium (1 ml peak at 1 Hz). Previously, CC was shown to facilitate and RA was shown to inhibit ACTH release. Electrical stimulation in the pons consisted of single shocks (500 microA DC, 0.05 msec, negative-to-tip) delivered on each of an array of three or four bipolar co-axial electrodes in the pons. Twenty-three neurons were tested with only RA. Of these, two were inhibited, two were facilitated, and 19 did not respond. Thirty-two neurons were tested with CC. Of these, nine were inhibited, nine were facilitated, and 14 did not respond. Seventeen neurons that responded either to RA or to CC were tested with stimulation in the pons. Of these, three were orthodromically activated and two were inhibited from a total of eight pontine sites. Six of the eight sites were within 300 microns of an area shown previously to contain neurons that responded to CC. Of 31 additional sites that were stimulated, but at which stimulation did not drive neurons that responded to hemodynamic stimuli, 26 were located more than 300 microns from this area (p less than 0.01, X2 test). The data suggest that some hypothalamic neurons involved in the hemodynamic control of ACTH release receive a projection from or through the dorsal raphe nucleus medially, and the ventral locus ceruleus, locus subceruleus, and underlying reticular formation laterally. However, other neurons may receive projections that bypass these regions.

Reflexes elicited by acute stretch of atrial vs. pulmonary receptors in conscious dogs.

We measured hemodynamics and renal function in conscious dogs while partially obstructing blood flow at various sites within the thorax. Inflation of a balloon in the left atrium increased left atrial pressure (LAP) by 9 mmHg and caused a parallel increase in pulmonary arterial pressure (PAP); heart rate, arterial pressure, and total peripheral resistance increased; stroke volume and right atrial pressure decreased; and cardiac output remained unchanged. The increase in LAP was accompanied by a fourfold increase in urine flow and a threefold increase in sodium excretion. Plasma vasopressin (AVP) and renin activity (PRA) decreased. On the other hand, partial occlusion of the pulmonary veins or the main pulmonary artery produced similar increases in PAP without affecting LAP, systemic hemodynamics, renal function, or plasma AVP. Similarly, inflation of a balloon in the right atrium failed to alter renal function, plasma AVP, or PRA. Finally, constriction of the thoracic inferior vena cava decreased LAP and increased PRA. In summary, these data emphasize that inflation of a balloon in the left atrium of the conscious dog produces a composite response consisting of alterations in cardiovascular function, renal function, and circulating hormones. Moreover, our data indicate that the response is mediated by a reflex initiated from receptors located in the left atrium; we detected no evidence that receptors located in the pulmonary vasculature or right heart contribute to this response.

Hypoxic pulmonary vasoconstriction and the pharmacologically denervated lung. Role of cardiac output and sympathetic nervous system.

Summary The roles of the autonomic nervous system and cardiac output on hypoxic pulmonary vasoconstriction were studied in 15 mongrel dogs anaesthetised with intravenous pentoharbitone (30 mg/kg) and the lungs mechanically ventilated to maintain normal arterial blood gases. After a hypoxic challenge in Group I (n =6) and Group II (n =3) animals, autonomic denervation was achieved by total spinal block with tetracaine (20 mg) injected into the cisterna magna. Group I animals received a large volume of intravenous fluid (80 ml/kg normal saline) before the block while Group II animals were given minimum fluid. When Group I animals were exposed to 10% inspired oxygen, mean pulmonary arterial pressure increased by 88 and by 72% before and after the block, respectively. The cardiac output increased by 27% with hypoxia before the block while it did not change significantly with hypoxia after the block. The pulmonary vascular resistance increased by 65 and by 152% with hypoxia before and after the block. Group II animals were also exposed to 10% inspired oxygen. They showed a similar response to Group I animals before the block. However, after the block irreversible hypotension developed with hypoxia. In Group III animals (n =6), the same anaesthesia and hypoxic challenge protocol was used. Immediately after measurements at 10 minutes of hypoxia, the inferior vena cava was constricted to reduce the cardiac output to the control level and another set of measurements were made. The cardiac output increased by 30% with hypoxia and then was reduced to the control level with vena caval constriction. The mean pulmonary arterial pressure increased by 125% with hypoxia and then it decreased slightly with the inferior vena cava constriction. The pulmonary vascular resistance increased by 95% with hypoxia and then it further increased by 28% with the vena caval constriction. These results suggest that sympathectomy accentuates rather than attenuates the hypoxic pulmonary vasoconstriction and that an increase in cardiac output counteracts hypoxic pulmonary vasoconstriction. The results also suggest that adequate intravascular volume and oxygenation are extremely important for maintaining homeostasis when reflex sympathetic stimulation to the cardiovascular system has been eliminated.

Kidney and liver function in rats during the edema following constriction of thoracic inferior vena cava with and without adrenalectomy or hypophysectomy.

In several animal species, constriction of the thoracic inferior vena cava (TIVCC) is known to increase proximal sodium reabsorption and inhibit natriuresis following saline loading, leading to edema. To eluicidate the role of adrenal and hypophyseal hormones in the development of edema, kidney and liver functions after TIVCC were compared in adrenalectomised or hypophysectomised rats, and in intact controls. It was found that edema (body weight increase) and kidney and liver affliction were much less pronounced after the operations. The roles of aldosterone and ADH deficiency in renal sodium and water excretion are discussed. It is concluded that adrenal and hypophyseal hormones do not initiate edema but modulate its extent. The absence of edematous changes in the liver of hypophysectomised and adrenalectomised rats deserves further attention.

Neurons in the dorsal rostral pons process information about changes in venous return and in arterial pressure

To examine pathways in the brain stem that process information from cardiovascular receptors we tested, in cats anesthetized with chloralose/urethane, 76 neurons in the locus coeruleus and locus subcoeruleus for their response to hemodynamic perturbations. The experiments were designed to define processing of information from arterial baroreceptors and from atrial receptors. We have modified the activity of baroreceptors and/or atrial receptors using partial constriction of the supradiaphragmatic inferior vena cava, with and without stabilization of arterial pressure and have modified the activity of atrial receptors directly using volume pulsation of the right atrium (+/- ml, 1 Hz, 3 min). The activity of 26 neurons increased and the activity of two neurons decreased in response to constriction of the vena cava. A quantitative analysis indicates that the behavior of these neurons is related in part to changes in arterial pressure and in part to changes in other pressures, such as atrial pressure. None of the neurons stimulated by constriction of the vena cava responded to volume pulsation of the right atrium. However, 6 of 9 responsive neurons tested responded also to contriction of the vena cava during stabilization of arterial pressure. Under this condition the neurons must be responding to changes in the activity of cardiovascular receptors other than arterial baroreceptors. The results suggest strongly that neurons in the locus coeruleus and locus subcoeruleus process information about changes in venous return and in arterial pressure. It is hypothesized that the responsive neurons may mediate changes in the release of pituitary hormones and in behavioral arousal in response to hemodynamic change.